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Apr 25, 2013 - A minute nonfunctioning pancreatic neuroendocrine tumor with lymph node metastasis. Yasuo Sakamoto • Kazuya Sakata • Shigeki Nakagawa ...
Int Canc Conf J (2014) 3:16–18 DOI 10.1007/s13691-013-0107-9

CASE REPORT

A minute nonfunctioning pancreatic neuroendocrine tumor with lymph node metastasis Yasuo Sakamoto • Kazuya Sakata • Shigeki Nakagawa • Daisuke Hashimoto • Yoshiaki Ikuta • Akira Chikamoto Masayuki Watanabe • Toru Beppu • Hideo Baba



Received: 14 February 2013 / Accepted: 11 April 2013 / Published online: 25 April 2013 Ó The Japan Society of Clinical Oncology 2013

Abstract The 2010 World Health Organization (WHO) classification proposed the grading of pancreatic neuroendocrine tumors (PNET) on the basis of proliferation, using the mitotic counts and/or Ki-67 index, although a surgical method according to grading has so far been indicated. Most patients with nonfunctioning PNET are not diagnosed until the appearance of tumor-related symptoms, because they have no hormonal symptoms, and the size of the tumor correlates well with its malignant potential in most cases. We herein present the case of a 67-year-old female with an asymptomatic very small pancreatic tumor. She was diagnosed as having nonfunctioning PNET on the basis of a cytological examination, and underwent a subtotal stomach-preserving pancreaticoduodenectomy. On the basis of histological examinations she was diagnosed as having a G1 PNET, 8 mm in diameter, with lymph node metastasis. Our findings suggest that standard surgery with substantial lymph node sampling should be performed for nonfunctioning PNET in order to ensure a complete resection, even if a tumor is minute and/or G1. Keywords Pancreatic neuroendocrine tumor  Lymph node metastasis  WHO classification

Introduction A pancreatic neuroendocrine tumor (PNET) is a comparatively rare tumor, which can be classified as functional or nonfunctional. PNETs are found in 0.5–1.5 % of autopsies, but are functional or symptomatic in less than 1 in 1,000 cases, thus resulting in a clinical detection rate of 1:100,000 population, which comprises 1–2 % of all pancreatic neoplasms [1]. The 2010 World Health Organization (WHO) classification proposed the grading of PNET on the basis of proliferation, using the mitotic count and/or Ki-67 index [2], although a surgical resection method according to grading has so far been indicated. Functional PNET is a clinical syndrome induced by excessive endocrine function. However, nonfunctioning PNETs do not result in the elevation of serum levels of pancreatic hormones or hormone-related symptoms and signs. Therefore, most patients with nonfunctioning PNET are not diagnosed until the appearance of tumor size-related symptoms, and the size of the tumor correlates well with its malignant potential in most cases. We herein present a case of nonfunctioning G1 PNET, which was 8 mm in diameter, with lymph node metastasis.

Case report

Y. Sakamoto (&)  K. Sakata  S. Nakagawa  D. Hashimoto  Y. Ikuta  A. Chikamoto  M. Watanabe  T. Beppu  H. Baba Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo Chuo-ku, Kumamoto 860-8556, Japan e-mail: [email protected] H. Baba e-mail: [email protected]

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A 67-year-old asymptomatic female was admitted to our hospital because abdominal ultrasonography revealed a tumor in the pancreatic head. Her serum levels of pancreatic hormones and tumor markers were within the normal ranges. The tumor had characteristic hypervascular features in abdominal enhanced computed tomography (Fig. 1a). Endoscopic ultrasonography-guided fine needle aspiration of the tumor revealed a nonfunctioning PNET. We performed a

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Fig. 1 a Abdominal CT showed an enhanced tumor (arrowhead). b The resected specimen showed a white tumor that measured 8 mm in diameter with a clear border

Fig. 2 a Less than 2 % of the cells were Ki-67-positive (HS stain, 9100). b Lymph node metastasis was detected in the posterior of the head of the pancreas (arrows)

subtotal stomach-preserving pancreaticoduodenectomy. A well-defined solid tumor, measuring 8 mm in diameter in the pancreatic head, was observed on the basis of macroscopic examinations of the specimen (Fig. 1b). Histological examinations diagnosed NET G1 with fewer than two mitotic cells per 10 HPF and less than 2 % Ki-67-positive cells (Fig. 2a), but lymph node metastases were found in the region posterior to the pancreatic head (Fig. 2b). The tumor cells were positive for chromogranin A, and negative for insulin, glucagon, gastrin, somatostatin, pancreatic peptide, and vasoactive intestinal peptide. The patient is still alive without recurrence as of 3 years after the surgery.

We recently treated a case of nonfunctioning PNET with lymph node metastasis, in spite of the fact that the patient had a G1 tumor measuring only 8 mm in diameter. The National Comprehensive Cancer Network (NCCN) guidelines recommend that, for small nonfunctioning PNET, the risks and benefits of a surgical resection should be carefully weighed, because the size of these tumors correlates well with their malignant potential. Lee et al. [6] reported that no disease progression or disease-specific mortalities were observed in 77 nonoperative patients with small nonfunctioning PNETs during a mean follow-up of 45 months, and concluded that nonoperative management of small nonfunctioning PNETs might be advocated. On the other hand, Kimura et al. [7] concluded, on the basis of their series of 125 nonfunctioning PNETs, that curative surgery should be performed to control primary nonfunctioning PNETs, with lymph node dissection recommended for nonfunctioning PNETs measuring 2.5 cm or larger and node sampling recommended for tumors with a diameter of 1 cm or more. Ikenaga et al. [8] reported a case of nonfunctioning PNET, which was 8 mm in diameter, that had invaded both the pancreatic parenchyma and the perineural spaces outside

Discussion PNETs are classified as functional or nonfunctional, and 50–80 % of PNETs are nonfunctioning [3]. Nonfunctioning PNETs are almost always clinically silent until they become huge or develop distant metastases, when they begin to cause abdominal pain, abdominal distention, obstructive jaundice, and/or intra-abdominal hemorrhage [4, 5].

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the tumor. Our present case was a minute nonfunctioning PNET with lymph node metastasis. These cases indicate that the surgical indications should be carefully considered, because nonfunctioning PNET possesses a histological malignant potential, even if it is smaller than 1 cm in diameter. An enucleation is often performed for a small pancreatic tumor, and safety and feasibility of the procedure have been reported [9, 10]. An enucleation is actually performed for benign tumors and especially insulinoma in PNETs [9]. However, because nonfunctioning PNETs often exhibit perineural invasion and lymph node metastasis, even if the tumor diameter is small, the curative resection of nonfunctioning PNETs achieves favorable results. In the present patient, no evidence of local recurrence or distant metastasis has been found during the 3-year follow-up after performing a complete resection. At present, the therapeutic strategies for treating small nonfunctioning PNETs have not yet been standardized. Considering that even 8-mm nonfunctioning PNETs have the potential for lymph node metastasis or perineural invasion, performing standard surgery with substantial lymph node sampling is justified, even in case of nonfunctioning PNETs with a diameter of 1 cm or less. Conflict of interest of interest.

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The authors declare that they have no conflict

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